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This paper examines the timing of one‐time fluctuations in births subsequent to the 1918 influenza pandemic in Madras (now Chennai), India. After seasonally decomposing key demographic aggregates, we identified abrupt one‐time fluctuations in excess births, deaths, and infant deaths. We found a contemporaneous spike in excess deaths and infant deaths and a 40‐week lag between the spike in deaths and a subsequent deficit in births. The results suggest that India experienced the same kind of short‐term postpandemic "baby bust" that was observed in the United States and other countries. Identifying the mechanisms underlying this widespread phenomenon remains an open question and an important topic for future research. [ABSTRACT FROM AUTHOR]

Background: The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2–13 (and 14–15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom. Methods: End‐of‐season adjusted vaccine effectiveness (VE) estimates against sentinel primary‐care attendance for influenza‐like illness, where influenza infection was laboratory confirmed, were calculated using the test negative design, adjusting for potential confounders. Methods: Results In the mainland United Kingdom, end‐of‐season VE against all laboratory‐confirmed influenza for all those > 65 years of age, most of whom received adjuvanted quadrivalent vaccines, was 30% (95% CI: −6% to 54%). VE for those aged 18–64, who largely received cell‐based vaccines, was 47% (95% CI: 37%–56%). Overall VE for 2–17 year olds, predominantly receiving live attenuated vaccines, was 66% (95% CI: 53%–76%). Conclusion: The paper provides evidence of moderate influenza VE in 2022/23. [ABSTRACT FROM AUTHOR]

Due to the extensive host range of influenza A viruses, it is difficult to determine the best diagnostic algorithm to efficiently screen samples from a variety of host species for influenza A viruses. While there are some influenza diagnostic algorithms that are specific to host species, to our knowledge, no single algorithm exists for the characterization of influenza A viruses across multiple host species. In this paper, we propose an algorithm that can serve as a guide for screening human, animal, and environmental samples for influenza A viruses of high human and animal health importance. [ABSTRACT FROM AUTHOR]

Background: We estimated combined protection conferred by prior SARS‐CoV‐2 infection and COVID‐19 vaccination against COVID‐19‐associated acute respiratory illness (ARI). Methods: During SARS‐CoV‐2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS‐CoV‐2 molecular testing and serology. Dried blood spots were tested for immunoglobulin‐G antibodies against SARS‐CoV‐2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS‐CoV‐2 infection also included documented or self‐reported laboratory‐confirmed COVID‐19. We used documented COVID‐19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status. Results: Four hundred fifty‐five (29%) of 1577 participants tested positive for SARS‐CoV‐2 infection at enrollment; 209 (46%) case‐patients and 637 (57%) test‐negative patients were NP seropositive, had documented previous laboratory‐confirmed COVID‐19, or self‐reported prior infection. Among previously uninfected patients, three‐dose VE was 97% (95% confidence interval [CI], 60%–99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three‐dose VE was 57% (CI, 20%–76%) against Omicron; VE against Delta could not be estimated. Conclusions: Three mRNA COVID‐19 vaccine doses provided additional protection against SARS‐CoV‐2 Omicron variant‐associated illness among previously infected participants. [ABSTRACT FROM AUTHOR]

Background: Public health and social measures (PHSM) intend to reduce the transmission of infectious diseases and to reduce the burden on health systems, economies and societies. During the COVID‐19 pandemic, PHSM have been selected, combined and implemented in a variable manner and inconsistently categorized in policy trackers. This paper presents an initial conceptual framework depicting how PHSM operate in a complex system, enabling a wide‐reaching description of these measures and their intended and unintended outcomes. Methods: In a multi‐stage development process, we combined (i) a complexity perspective and systems thinking; (ii) literature on existing COVID‐19 PHSM frameworks, taxonomies and policy trackers; (iii) expert input and (iv) application to school and international travel measures. Results: The initial framework reflects our current understanding of how PHSM are intended to achieve transmission‐related outcomes in a complex system, offering visualizations, definitions and worked examples. First, PHSM operate through two basic mechanisms, that is, reducing contacts and/or making contacts safer. Second, PHSM are defined not only by the measures themselves but by their stringency and application to specific populations and settings. Third, PHSM are critically influenced by contextual factors. The framework provides a tool for structured thinking and further development, rather than a ready‐to‐use tool for practice. Conclusions: This conceptual framework seeks to facilitate coordinated, interdisciplinary research on PHSM effectiveness, impact and implementation; enable consistent, coherent PHSM monitoring and evaluation; and contribute to evidence‐informed decision‐making on PHSM implementation, adaptation and de‐implementation. We expect this framework to be modified and refined over time. [ABSTRACT FROM AUTHOR]

Background: Rapid reporting of surveillance data is essential to better inform national prevention and control strategies. Objectives: We compare the newly implemented smartphone‐based system to the former paper‐based and short message service (SMS) for collecting influenza epidemiological data in Cameroon. Methods: Of the 13 sites which collect data from persons with influenza‐like illness (ILI), six sites send data through the EWS, while seven sites make use of the paper‐based system and SMS. We used four criteria for the comparison of the data collection tools: completeness, timeliness, conformity and cost. Results: Regarding the different collection tools, data sent by the EWS were significantly more complete (97.6% vs 81.6% vs 44.8%), prompt (74.4% vs n/a vs 60.7%) and of better quality (93.7% vs 76.1% vs 84.0%) than data sent by the paper‐based system and SMS, respectively. The average cost of sending a datum by a sentinel site per week was higher for the forms (5.0 USD) than for the EWS (0.9 USD) and SMS (0.1 USD). The number of outpatient visits and subsequently all surveillance data decreased across the years 2017‐2019 together with the influenza positivity rate from 30.7% to 28.3%. Contrarily, the proportion of influenza‐associated ILI to outpatient load was highest in the year 2019 (0.37 per 100 persons vs 0.28 and 0.26 in the other 2 years). Conclusion: All sentinel sites and even other disease surveillance systems are expected to use this tool in the near term future due to its satisfactory performance and cost. [ABSTRACT FROM AUTHOR]

Background: External quality assessments (EQAs) for the molecular detection of respiratory syncytial virus (RSV) are necessary to ensure the provision of reliable and accurate results. One of the objectives of the pilot of the World Health Organization (WHO) Global RSV Surveillance, 2016‐2017, was to evaluate and standardize RSV molecular tests used by participating countries. This paper describes the first WHO RSV EQA for the molecular detection of RSV. Methods: The WHO implemented the pilot of Global RSV Surveillance based on the WHO Global Influenza Surveillance and Response System (GISRS) from 2016 to 2018 in 14 countries. To ensure standardization of tests, 13 participating laboratories were required to complete a 12 panel RSV EQA prepared and distributed by the Centers for Disease Control and Prevention (CDC), USA. The 14th laboratory joined the pilot late and participated in a separate EQA. Laboratories evaluated a RSV rRT‐PCR assay developed by CDC and compared where applicable, other Laboratory Developed Tests (LDTs) or commercial assays already in use at their laboratories. Results: Laboratories performed well using the CDC RSV rRT‐PCR in comparison with LDTs and commercial assays. Using the CDC assay, 11 of 13 laboratories reported correct results. Two laboratories each reported one false‐positive finding. Of the laboratories using LDTs or commercial assays, results as assessed by Ct values were 100% correct for 1/5 (20%). With corrective actions, all laboratories achieved satisfactory outputs. Conclusions: These findings indicate that reliable results can be expected from this pilot. Continued participation in EQAs for the molecular detection of RSV is recommended. [ABSTRACT FROM AUTHOR]

Background: The burden of influenza in primary care is difficult to assess, since most patients with symptoms of a respiratory infection are not tested. The case definition of "medically attended acute respiratory infection" (MAARI) in the German physician sentinel is sensitive; however, it requires modelling techniques to derive estimates of disease attributable to influenza and respiratory syncytial virus (RSV). Objectives: The objective of this paper was to review and extend our previously published model in order to estimate the burden of RSV and the differential burden of the two influenza B lineages (Victoria, Yamagata) as well as both influenza A subtypes on primary care visits. Methods: Data on MAARI and virological results of respiratory samples (virological sentinel) were available from 2010/11 until 2017/18. We updated the previously published generalized additive regression model to include RSV. Results: We found that the proportion of MAARI due to RSV is substantial only in the 0‐1‐ and 2‐4‐year‐old age groups (0‐1 years old: median 7.5%, range 4.0%‐14.8%; 2‐4 years old: median 6.5%, range 4.0%‐10.3%); in the 0‐1 years old age group, RSV leads in almost all seasons to a higher burden than any influenza type or subtype, but this is reversed in the age group 2‐4 years old. Conclusions: We succeeded in rearranging our previously published model on MAARI to incorporate RSV as well as the two influenza B lineages (Victoria, Yamagata) in the time period 2010 to 2018. [ABSTRACT FROM AUTHOR]

Influenza vaccine safety is an ongoing issue. In 2010, inactivated trivalent influenza vaccines (TIVs), Fluvax® and Fluvax Junior® manufactured by CSL Biotherapies ('CSL'), Parkville, Australia, were associated with a marked increase in febrile seizures (FS) in children <5 years old. Extensive investigations initially failed to identify a root cause. The company's researchers recently published two papers outlining their latest findings. Cytokine responses to TIV were measured in paediatric whole blood assays (WBA); NF-μB activation was assessed using a HEK293 cell line reporter assay. CSL suggest that the combination of new influenza strains (H1N1 A/California/7/2009 and B/Brisbane/60/2008), increased complexes of viral RNA and lipid in the vaccine, and inherent sensitivities of some children <5 years old caused elevated inflammatory responses resulting in FS. Whilst the papers provide insight into pathogenesis, much remains unclear. The WBA were from only 10 'healthy' children, potentially affecting generalisability of the results and reliability of these in vitro tests in assessing future influenza vaccine safety. Increased fever rates (without FS) found in CSL TIV studies between 2005 and 2010 suggest a long-standing contribution to reactogenicity from the manufacturing process. More detailed comparisons with non-CSL vaccines would have helped elucidate the relative contribution of patient/strain factors and the manufacturing process. The focus remains on manufacturing process differences as the key causative factor of elevated febrile responses. Studies underway, of modified vaccines in young children, will determine whether reactogenicity issues have been successfully addressed and whether CSL TIV can be relicensed in children <5 years of age. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Cornwell B. (2012) Unemployment and widespread influenza in America, 1999-2010. Influenza and Other Respiratory Viruses 6(1), 63-70. Background Research shows that unemployment reduces access to health care and vaccines and increases financial difficulty, family conflict, and other sources of stress that are known to suppress immune function. In addition, seasonal unemployment rates parallel seasonal influenza activity. Following a theory that argues that macroeconomic conditions affect population health, this paper examines whether there is an association between monthly unemployment rates and influenza activity. Methods Data from influenza activity surveillance reports from the Centers for Disease Control and Prevention are combined with information from the Bureau of Labor Statistics on state-level unemployment rates in the U.S. for the flu seasons between 1999 and 2010. Pooled time-series cross-section logistic regression analyses are conducted to examine the effect of the unemployment rate on the likelihood of widespread and/or regional influenza activity in the 48 contiguous states throughout this period. A total of 3712 state-month observations are examined. Results Net of other factors included in the multivariate regression analysis, a one-percentage-point increment in the unemployment rate is associated with between a 7·1% and 37·0% increment in the odds of widespread influenza (Odds ratio = 1·21). Likewise, a one-percentage-point increment in the unemployment rate is associated with between a 17·1% and 44·7% increment in the odds of at least regional influenza (Odds ratio = 1·30). Results hold regardless of whether time-varying state-level characteristics are included. Conclusions Higher state-level unemployment increases the likelihood of regional and widespread influenza activity. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Devroey et al. (2011) Online monitoring of flu in Belgium. Influenza and Other Respiratory Viruses 5(5), 351-356. Background The diagnosis and treatment of patients with the A(H1N1) pandemic flu caused some serious burden for general practitioners (GPs) in the summer and autumn of 2009. Objective The aim of this study was to track the incidence of influenza and influenza-like illness (ILI) in Belgium and to describe the characteristics of the affected patients. Methods In July 2009, the Belgian online influenza surveillance system (BOISS) was set up to monitor the spread of influenza and ILI. Registrations were made by 93 GPs from all 10 Belgian provinces who participated at least 1 week during the first 12 months of the registration. Only patients who met the WHO criteria for flu were recorded. Results In total, 1254 patients (53% men) with influenza or ILI were included. Mainly younger persons were affected: 43% was under the age of 20 years. A risk factor for influenza-related complications was determined in 19% of cases, mainly patients with chronic respiratory problems. A treatment with oseltamivir or zanamivir was prescribed in 13%, and 3% of the patients was admitted to a hospital. The time of the peak incidence (44th week) and the magnitude (623 cases per week per 100 000 inhabitants) corresponded with the figures of the existing paper-based registration network. The small sample size and possible reporting biases may have influenced the findings of the study. Conclusions The BOISS provides a good alternative to conduct surveillance activities for influenza and ILI in Belgium. It provides complementary information regarding ILI compared to the existing data capturing. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Simmerman et al. (2011) Findings from a household randomized controlled trial of hand washing and face masks to reduce influenza transmission in Bangkok, Thailand. Influenza and Other Respiratory Viruses 5(4), 256-267 Evidence is needed on the effectiveness of non-pharmaceutical interventions (NPIs) to reduce influenza transmission. We studied NPIs in households with a febrile, influenza-positive child. Households were randomized to control, hand washing (HW), or hand washing plus paper surgical face masks (HW + FM) arms. Study nurses conducted home visits within 24 hours of enrollment and on days 3, 7, and 21. Respiratory swabs and serum were collected from all household members and tested for influenza by RT-PCR or serology. Between April 2008 and August 2009, 991 (16·5%) of 5995 pediatric influenza-like illness patients tested influenza positive. Four hundred and forty-two index children with 1147 household members were enrolled, and 221 (50·0%) were aged <6 years. Three hundred and ninety-seven (89·8%) households reported that the index patient slept in the parents' bedroom. The secondary attack rate was 21·5%, and 56/345 (16·3%; 95% CI 12·4-20·2%) secondary cases were asymptomatic. Hand-washing subjects reported 4·7 washing episodes/day, compared to 4·9 times/day in the HW + FM arm and 3·9 times/day in controls ( P = 0·001). The odds ratios (ORs) for secondary influenza infection were not significantly different in the HW arm (OR = 1·20; 95% CI 0·76-1·88; P-0.442), or the HW + FM arm (OR = 1·16; 95% CI .0·74-1·82; P = 0.525). Influenza transmission was not reduced by interventions to promote hand washing and face mask use. This may be attributable to transmission that occurred before the intervention, poor facemask compliance, little difference in hand-washing frequency between study groups, and shared sleeping arrangements. A prospective study design and a careful analysis of sociocultural factors could improve future NPI studies. [ABSTRACT FROM AUTHOR]

Aim Coinfecting bacterial pathogens are a major cause of morbidity and mortality in influenza. However, there remains a paucity of literature on the magnitude of coinfection in influenza patients. Method A systematic search of Me SH, Cochrane Library, Web of Science, SCOPUS, EMBASE, and PubMed was performed. Studies of humans in which all individuals had laboratory confirmed influenza, and all individuals were tested for an array of common bacterial species, met inclusion criteria. Results Twenty-seven studies including 3215 participants met all inclusion criteria. Common etiologies were defined from a subset of eight articles. There was high heterogeneity in the results ( I 2 = 95%), with reported coinfection rates ranging from 2% to 65%. Although only a subset of papers were responsible for observed heterogeneity, subanalyses and meta-regression analysis found no study characteristic that was significantly associated with coinfection. The most common coinfecting species were Streptococcus pneumoniae and Staphylococcus aureus, which accounted for 35% (95% CI, 14%-56%) and 28% (95% CI, 16%-40%) of infections, respectively; a wide range of other pathogens caused the remaining infections. An assessment of bias suggested that lack of small-study publications may have biased the results. Conclusions The frequency of coinfection in the published studies included in this review suggests that although providers should consider possible bacterial coinfection in all patients hospitalized with influenza, they should not assume all patients are coinfected and be sure to properly treat underlying viral processes. Further, high heterogeneity suggests additional large-scale studies are needed to better understand the etiology of influenza bacterial coinfection. [ABSTRACT FROM AUTHOR]

Objectives To review neurological complications after the influenza A (H1N1) pdm09, highlighting the clinical differences between patients with post-vaccine or viral infection. Design A search on Medline, Ovid, EMBASE, and PubMed databases using the keywords 'neurological complications of Influenza AH1N1' or 'post-vaccine Influenza AH1N1.' Setting Only papers written in English, Spanish, German, French, Portuguese, and Italian published from March 2009 to December 2012 were included. Sample We included 104 articles presenting a total of 1636 patient cases. In addition, two cases of influenza vaccine-related neurological events from our neurological care center, arising during the period of study, were also included. Main outcome measures Demographic data and clinical diagnosis of neurological complications and outcomes: death, neurological sequelae or recovery after influenza A (H1N1) pdm09 vaccine or infection. Results The retrieved cases were divided into two groups: the post-vaccination group, with 287 patients, and the viral infection group, with 1349 patients. Most patients in the first group were adults. The main neurological complications were Guillain-Barre syndrome ( GBS) or polyneuropathy (125), and seizures (23). All patients survived. Pediatric patients were predominant in the viral infection group. In this group, 60 patients (4.7%) died and 52 (30.1%) developed permanent sequelae. A wide spectrum of neurological complications was observed. Conclusions Fatal cases and severe, permanent, neurological sequelae were observed in the infection group only. Clinical outcome was more favorable in the post-vaccination group. In this context, the relevance of an accurate neurological evaluation is demonstrated for all suspicious cases, as well as the need of an appropriate long-term clinical and imaging follow-up of infection and post-vaccination events related to influenza A (H1N1) pdm09, to clearly estimate the magnitude of neurological complications leading to permanent disability. [ABSTRACT FROM AUTHOR]

Forecasting the dynamics of influenza outbreaks could be useful for decision-making regarding the allocation of public health resources. Reliable forecasts could also aid in the selection and implementation of interventions to reduce morbidity and mortality due to influenza illness. This paper reviews methods for influenza forecasting proposed during previous influenza outbreaks and those evaluated in hindsight. We discuss the various approaches, in addition to the variability in measures of accuracy and precision of predicted measures. Pub Med and Google Scholar searches for articles on influenza forecasting retrieved sixteen studies that matched the study criteria. We focused on studies that aimed at forecasting influenza outbreaks at the local, regional, national, or global level. The selected studies spanned a wide range of regions including USA, Sweden, Hong Kong, Japan, Singapore, United Kingdom, Canada, France, and Cuba. The methods were also applied to forecast a single measure or multiple measures. Typical measures predicted included peak timing, peak height, daily/weekly case counts, and outbreak magnitude. Due to differences in measures used to assess accuracy, a single estimate of predictive error for each of the measures was difficult to obtain. However, collectively, the results suggest that these diverse approaches to influenza forecasting are capable of capturing specific outbreak measures with some degree of accuracy given reliable data and correct disease assumptions. Nonetheless, several of these approaches need to be evaluated and their performance quantified in real-time predictions. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Mahmud et al. (2012) Outbreaks of influenza-like illness in long-term care facilities in Winnipeg, Canada. Influenza and Other Respiratory Viruses 10.1111/irv.12052 Background Outbreaks of influenza-like illness (ILI) are common in long-term care facilities (LTCFs) and result in significant morbidity and mortality among residents. Objectives We describe patterns of reported ILI outbreaks in LTCFs in Winnipeg, Canada, and examine LTCF and outbreak characteristics that influence the clinical outcomes of these outbreaks. Methods We analyzed the electronic records of all ILI outbreaks reported by LTCFs in Winnipeg from 2003 to 2011. Outbreak duration, ILI attack rates among staff and residents, and residents' death rates were calculated by presumed viral etiology, staff vaccination rates, type of influenza chemoprophylaxis used, and time to notification to public health. Results Of a total of 154 reported outbreaks, most ( N = 80) were attributed to influenza, and these outbreaks tended to have higher attack and death rates among LTCF residents compared with outbreaks caused by other respiratory viruses (12) or those of unknown etiology (62). About 92% of residents and 38% of staff of the average LTCFs were vaccinated. Chemoprophylaxis was used in 57·5% of influenza outbreaks. Regardless of presumed viral etiology, outbreaks reported within 3 days of onset ended sooner and had lower attack and mortality rates among residents. Conclusions Influenza-like illness outbreaks still occur among highly immunized LTCF residents, so in addition to vaccination of staff and residents, it is important to maintain competent infection control practices. Early identification and notification to public health authorities and possibly early initiation of control measures could improve clinical outcomes of ILI outbreaks. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Lohiniva et al. (2012) Poultry rearing and slaughtering practices in rural Egypt: an exploration of risk factors for H5N1 virus human transmission. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12023. Background Highly pathogenic avian influenza (H5N1) virus continues to cause infections in Egypt. This study describes the practices associated with raising and slaughtering household poultry to identify risk factors for H5N1 infection and reasons for non-compliance with preventive measures. Methods An investigation was conducted of 56 households with household flocks (19 households with human H5N1 cases, 19 with poultry H5N1 cases, and 18 with no reported poultry or human H5N1 cases). Data were collected via structured observations and in-depth interviews. Results Half of the households kept at least some free-range poultry and mixed at least some different species of poultry as it was considered beneficial for the poultry. Feeding and cleaning practices exposed children to contact with poultry; slaughtering contaminated homes; use of personal protective barriers was not a norm; waste management exposed the communities to slaughtering waste and dead chickens; and reporting of sick and dead poultry was not a practice. Only minor changes in poultry-handling took place following H5N1 virus outbreaks. Discussion H5N1 virus prevention in Egypt represents both an epidemiological and socio-cultural challenge. Traditional poultry-rearing practices that likely increase exposures to H5N1-infected poultry are common throughout Egypt. Despite education campaigns following sporadic H5N1 outbreaks, no differences in these practices could be detected between households with previous H5N1 human or poultry cases and those households with any previous experience with H5N1. Development of H5N1 infection-related education campaign strategies should focus on perceptions underlying traditional practices in order to tailor public awareness messages that are meaningful for communities. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Larcombe et al. (2012) Factors influencing the assessment of lung function in mice with influenza-induced lung disease. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12034. Background The constant-phase model (CPM) is commonly fit to respiratory system input impedance ( Zrs) to estimate lung mechanics. Driving signal frequencies and the method of model fitting may influence the results, especially in cases of severe lung disease or under severe bronchoconstriction. Objective To illustrate the effects of different CPM fits to Zrs data using a mouse model of influenza-induced lung disease. Methods BALB/c mice infected with influenza (or control) were challenged with methacholine. The CPM was fitted to Zrs, measured between 0·25 and 19·625 Hz, using both unweighted and weighted fits. The effect of different lowest frequencies was assessed. Results and Conclusions For influenza-infected mice, the unweighted fit was poor, and airway resistance ( Raw) was often biologically impossible. The weighted fit provided more realistic estimates of Raw. Different model fits and minimal frequencies had little effect on tissue mechanics. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Svindland et al. (2012) A study of Chitosan and c-di-GMP as mucosal adjuvants for intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses 10.1111/irv.12056000(000), 000-000. Background Highly pathogenic avian influenza A/H5N1 virus remains a potential pandemic threat, and it is essential to continue vaccine development against this subtype. A local mucosal immune response in the upper respiratory tract may stop influenza transmission. It is therefore important to develop effective intranasal pandemic influenza vaccines that induce mucosal immunity at the site of viral entry. Objectives We evaluated the humoral and cellular immune responses of two promising mucosal adjuvants (Chitosan and c-di-GMP) for intranasal influenza H5N1 vaccine in a murine model. Furthermore, we evaluated the concept of co-adjuvanting an experimental adjuvant (c-di-GMP) with chitosan. Methods BALB/c mice were intranasally immunised with two doses of subunit NIBRG-14 (H5N1) vaccine (7·5, 1·5 or 0·3 μg haemagglutinin (HA) adjuvanted with chitosan (CSN), c-di-GMP or both adjuvants. Results All adjuvant formulations improved the serum and local antibody responses, with the highest responses observed in the 7·5 μg HA CSN and c-di-GMP-adjuvanted groups. The c-di-GMP provided dose sparing with protective single radial haemolysis (SRH), and haemagglutination inhibition (HI) antibody responses found in the 0·3 μg HA group. CSN elicited a Th2 response, whereas c-di-GMP induced higher frequencies of virus-specific CD4+ T cells producing one or more Th1 cytokines (IFN-γ+, IL-2+, TNF-α+). A combination of the two adjuvants demonstrated effectiveness at 7·5 μg HA and triggered a more balanced Th cytokine profile. Conclusion These data show that combining adjuvants can modulate the Th response and in combination with ongoing studies of adjuvanted intranasal vaccines will dictate the way forward for optimal mucosal influenza vaccines. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Sheldon et al. (2013) Immunogenicity of a quadrivalent Ann Arbor strain live attenuated influenza vaccine delivered using a blow-fill-seal device in adults: a randomized, active-controlled study. Influenza and Other Respiratory Viruses 7(6), 1142-1150. Background Influenza B strains from two distinct lineages (Yamagata and Victoria) have cocirculated over recent years. Current seasonal vaccines contain a single B lineage resulting in frequent mismatches between the vaccine strain and the circulating strain. An Ann Arbor strain quadrivalent live attenuated influenza vaccine (Q/LAIV) containing B strains from both lineages is being developed to address this issue. Objectives The goal of this study was to evaluate whether Q/LAIV administered intranasally as a single dose to a single nostril, using a blow-fill-seal (BFS) delivery system had a similar immunogenicity and safety profile compared with the licensed trivalent vaccine delivered using the Accuspray device. Patients/Methods Adults aged 18-49 years were randomized to receive one intranasal dose of Q/LAIV delivered using a BFS device (Q/LAIV-BFS; n = 1202) or one of two trivalent live attenuated influenza vaccines (T/LAIV) containing one of the corresponding B strains (total T/LAIV, n = 598). Primary endpoints were the post-vaccination strain-specific serum hemagglutination inhibition antibody geometric mean titers for each strain. Secondary immunogenicity endpoints, safety, and acceptability of the BFS device were also assessed. Results Q/LAIV was immunogenically non-inferior to T/LAIV for all four influenza strains. Secondary immunogenicity outcomes were consistent with the primary endpoint. Solicited symptoms and AEs were comparable in both groups. Subjects considered the BFS device to be acceptable. Conclusions Immune responses to vaccination with Ann Arbor strain Q/LAIV-BFS were non-inferior to those with T/LAIV. Q/LAIV may confer broader protection against seasonal influenza B by targeting both major influenza B lineages. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Vuong et al. (2013). The genetic match between vaccine strains and circulating seasonal influenza A viruses in Vietnam, 2001-2009. Influenza and Other Respiratory Viruses 7(6), 1151-1157. Background Vietnam is currently developing domestic capability to manufacture influenza vaccines but information on the genetic and antigenic characteristics of locally circulating seasonal influenza viruses is limited. To assess the relevance of WHO recommended vaccine strains to the situation in Vietnam, we analyzed the genetic relatedness of the hemagglutinin (HA) gene of seasonal influenza A viruses circulating in Vietnam from 2001 to 2009 to WHO recommended vaccine strains over the same period. Methods and Principal findings We sequenced the HA gene of 32 H1N1 and 44 H3N2 seasonal influenza A isolates from laboratory-based sentinel surveillance sites in Hanoi from 2001 to 2005 and from a national influenza surveillance system from 2005 to 2009. H1 and H3 HA phylogenetic trees rooted to vaccine strains A/Beijing/295/1995 (H1N1) and A/Moscow/10/1999 (H3N2), respectively, were constructed with contemporary HA sequences of isolates from neighboring countries. We found some genetic differences between seasonal influenza H3N2 viruses and three WHO influenza vaccine strains recommended for use in the Northern and Southern Hemispheres for the 2001-2004 and 2007-2008 seasons and close genetic identity of circulating H3N2 strains with the recommended WHO Southern Hemisphere vaccine strains for 2004 and 2009 seasons. The genetic similarity of circulating H1N1 strains with the WHO recommended vaccine strains are described for the study period 2001-2009. Conclusions The HA gene of seasonal influenza virus strains in Vietnam (especially influenza A/H3N2) showed varying degrees of genetic identity compared with those of the Northern or Southern Hemisphere vaccine strains recommended by WHO. The close relatedness of the HA of Vietnamese strains and contemporary strains from nearby countries indicate a good genetic match of circulating strains during study period. Greater representation of virus isolates from South East Asia in the vaccine strain selection process is desirable of influenza vaccine development in Vietnam. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Starbuck et al (2012) Are we prepared to help low-resource communities cope with a severe influenza pandemic? Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12040. Recent research involving lab-modified H5N1 influenza viruses with increased transmissibility and the ongoing evolution of the virus in nature should remind us of the continuing importance of preparedness for a severe influenza pandemic. Current vaccine technology and antiviral supply remain inadequate, and in a severe pandemic, most low-resource communities will fail to receive adequate medical supplies. However, with suitable guidance, these communities can take appropriate actions without substantial outside resources to reduce influenza transmission and care for the ill. Such guidance should be completed, and support provided to developing countries to adapt it for their settings and prepare for implementation. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Memoli et al. (2012) Influenza in pregnancy. Influenza and Other Respiratory Viruses 00(00), 000-000. The 2009 pandemic served as a strong reminder that influenza-induced disease can have a great impact on certain at-risk populations and that pregnant women are one such important population. The increased risk of fatal and severe disease in these women was appreciated more than 500 years ago, and during the last century, pregnant women and their newborns have continued to be greatly affected by both seasonal and pandemic influenza. In this review, we briefly discuss the data collected both before and after the 2009 pandemic as it relates to the impact of influenza on pregnant women and their fetuses/newborns, as well as risk variables, clinical features, clues to pathophysiologic mechanisms, and approaches to treatment and prevention. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Kim et al. (2012) Characteristics of respiratory viral infections during influenza season in Canadian Hutterite Communities. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12021. Objectives: To determined the pathogen-specific incidence of respiratory virus infection in Hutterite communities occurring over the 2008-2009 influenza season and assess temporal characteristics of respiratory illness related to infection. Methods: 3273 participants community members enrolled in a cluster randomized trial of influenza vaccine were studied. Results: One hundred forty-nine participants had laboratory-confirmed influenza, and 595 had at least one episode of laboratory-confirmed respiratory viral infection other than influenza. Entero/rhinovirus had the highest incidence among children <5 years. Conclusions: A decline in the incidence of infections with age was observed for influenza as well as for most other respiratory viruses. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Basurto-Dávila et al. (2012) Household economic impact and attitudes toward school closures in two cities in Argentina during the 2009 influenza A (H1N1) pandemic. Influenza and Other Respiratory Viruses. DOI: 10.1111/irv.12054. Background School closures were widely implemented in Argentina during the 2009 H1N1 influenza virus pandemic. Objectives To assess the economic impact of school closures on households, their effectiveness in preventing children from engaging in social group activities, and parental attitudes toward them. Methods Three schools that closed for 2 weeks in response to the pandemic were identified in two socioeconomically distinct cities in Argentina. All households with children enrolled in these schools were surveyed. Direct and indirect costs attributable to closures were estimated from the household perspective. Other information collected included children activities during the closures and parental attitudes toward the intervention. Results Completed questionnaires were returned by 45% of surveyed households. Direct and indirect costs due to closures represented 11% of imputed monthly household income in the city with lower socioeconomic status, and 3% in the other city ( P = 0·01). Non-childcare expenses and loss of workdays were more common in the city with lower socioeconomic status. Childcare expenses were less common and were experienced by a similar percentage of households in both cities. About three-quarters of respondents in both cities agreed with the closures. The main concern among those who disagreed with closures was their negative impact on education. Children in more than two-thirds of affected households left their home at least once during the closures to spend time in public places. Conclusion School closures may more significantly impact low-income households. Authorities should consider the range of economic impacts of school closures among families when planning their implementation. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Savy et al. (2012) Burden of influenza in Latin America and the Caribbean: a systematic review and meta-analysis. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12036. Objective Influenza causes severe morbidity and mortality. This systematic review aimed to assess the incidence, etiology, and resource usage for influenza in Latin America and the Caribbean. Design Meta-analytic systematic review. Arcsine transformations and DerSimonian Laird random effects model were used for meta-analyses. Setting A literature search from 1980 to 2008 in MEDLINE, Cochrane Library, EMBASE, LILACS, Ministries of Health, PAHO, proceedings, reference lists, and consulting experts. Sample We identified 1092 references, of which 31 were finally included, in addition to influenza surveillance reports. We also used information from the 10 reports from the collaborative group for epidemiological surveillance of influenza and other respiratory virus (GROG), and information retrieved from the WHO global flu database FLUNET. Main outcome measures Incidence, percentage of influenza specimens out of the total received by influenza centers and resource-use outcomes. Results A total of 483 130 specimens of patients with influenza were analyzed. Meta-analysis showed an annual rate of 36 080 (95%CI 28 550 43 610) influenza-like illness per 100 000 persons-years. The percentage of influenza out of total specimens received by influenza centers ranged between 4.66% and 15.42%, with type A the most prevalent, and A subtype H3 predominating. The mean length of stay at hospital due to influenza ranged between 5.8 12.9 days, total workdays lost due to influenza-like illnesses were 17 150 days, and the mean direct cost of hospitalization was US$575 per laboratory-confirmed influenza case. Conclusions Our data show that seasonal influenza imposes a high morbidity and economic burden to the region. However, the vaccine-uptake rate has been low in this region. Population-based cohort studies are required to improve the knowledge about incidence and resource utilization, which would inform healthcare authorities for decision making. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Kersun et al. (2013) A prospective study of chemotherapy immunologic effects and predictors of humoral influenza vaccine responses in a pediatric oncology cohort. Influenza and Other Respiratory Viruses 7(6), 1158-1167. Background: Pediatric oncology patients represent a cohort of individuals uniquely at risk of complications from influenza, yet less likely to respond to the vaccine. It is not yet clear how to best protect this vulnerable population. Methods: We performed a prospective analysis of 177 pediatric oncology patients to define the predictors of influenza vaccine responses. Each variable was examined over three time points and a repeated measure analysis was performed. Results: Patients with ALL vaccinated during induction phase had superior influenza vaccine responses than those subjects vaccinated during post-induction or maintenance phases ( P = 0·0237). Higher aggregate HAI titer responses were associated with a higher baseline B-cell count ( P = 0·0240), and higher CD4 and CD8 influenza-specific T-cell responses, suggesting prior antigen exposure is a significant contributor. The solid tumor cohort had equivalent responses during all time frames of chemotherapy. Discussion: The optimal protection from influenza of pediatric patients on chemotherapy should include vaccination, but it is clear that not all patients produce high titers of antibodies after vaccination. This study identified biomarkers that could be used to individualize vaccine approaches. Immunologic predictors might have a role in targeting resources, as B-cell counts predicted of vaccine responses among the patients with ALL. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Goka et al. (2013) Influenza A viruses dual and multiple infections with other respiratory viruses and risk of hospitalisation and mortality. Influenza and Other Respiratory Viruses 7(6), 1079-1087. Introduction Recent literature suggests that dual or multiple virus infections may affect disease severity. However, few studies have investigated the effect of co-infection with influenza A viruses. Objectives To identify the association between influenza A and respiratory viruses co-infections with disease outcome. Methodology Data for samples from North West England tested between January 2007 and June 2011 was analysed for patterns of co-infection between influenza A viruses and eight respiratory viruses. Risk of hospitalisation to ICU or general ward in single versus co-infections was assessed using logistic regression. Results Of the 25 596 samples analysed for respiratory viruses 40·7% (10 501) were positive for any virus. Co-infections were detected in 4·7% (137/2879) of all patients with influenza A(H1N1)pdm09, and 7·3% (57/779) of those with other influenza A virus infections. Co-infection between seasonal influenza A viruses and influenza B virus was associated with a significant increase in the risk of admission to ICU/death (OR: 22·0, 95% CI: 2·21-219·8, P = 0·008). Respiratory syncytial virus/influenza A (RSV/Flu A) co-infection also increased this risk but was not statistically significant. For influenza A(H1N1)pdm09, RSV and AdV co-infection increased risk of hospitalisation to general ward whereas Flu B increased risk of admission to ICU, but none of these were statistically significant. Conclusion Co-infection is a significant predictor of disease outcome; combined treatment, introduction of an integrated vaccine for all respiratory viruses and development of multi-target rapid diagnostic tests is recommended. Integration of respiratory viruses' co-infections into public health reports could also contribute to the accumulation of evidence. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Obasi et al. (2012) Advantage of meditation over exercise in reducing cold and flu illness is related to improved function and quality of life. Influenza and Other Respiratory Viruses 00(0), 00-00. Purpose To examine whether apparent advantages following training in meditation over exercise can be attributed to specific symptoms, functional impairments, or quality-of-life indicators assessed by the Wisconsin Upper Respiratory Symptom Survey (WURSS-24). Methods Results from the randomized controlled trial 'Meditation or Exercise for Preventing Acute Respiratory Illness' showed mean global severity and total days of illness were worse in control (358, 8·9) compared with exercise (248, 5·1) or meditation (144, 5·0). Global severity of illness was estimated using area under the curve from daily self-reported severity scores on the WURSS-24. For this project, we estimated within-group WURSS item-level severity and between-group effect sizes (Cohen's ' d' statistic ) relative to control. The item-level effect sizes were grouped into (i) symptom and (ii) function and quality of life domains. Results Among the three groups, mediators showed the lowest severity estimates for 21 of 22 WURSS items. Item-level Cohen's ' d' indicated most benefit was evident in WURSS items representing function and quality of life. Compared with exercise, meditation fostered larger reductions in illness severity, although due mostly to improved function and the quality of life domain ( d = −0·33, P < 0·001) compared with symptom domain ( d = −0·22, P < 0·001). Conclusions The apparent advantage of training in meditation over exercise for reducing cold and flu illness is explained more by improved function and quality of life than by a reduction in symptom severity. [ABSTRACT FROM AUTHOR]

Please cite this paper as: He et al. (2013) Amaryllidaceae alkaloids inhibit nuclear-to-cytoplasmic export of ribonucleoprotein (RNP) complex of highly pathogenic avian influenza virus H5N1. Influenza and Other Respiratory Viruses 7(6), 922-931. Background Few drugs are currently licensed to treat influenza A infection, and new therapies are needed, especially for highly pathogenic strains. Traditional medicinal plants, such as Lycoris radiata, are a potential source of new antiviral agents. Objective To test 15 Amaryllidaceae alkaloids isolated from the bulbs of L. radiata in vitro for antiviral activities against influenza virus type A, A/Chicken/GuangDong/178/2004 (H5N1, 178). Methods Antiviral activities of the compounds were tested in time-of-addition assays, hemagglutination inhibition (HI) assays, neuraminidase (NA) activity assays, and viral entry inhibition assays using H5N1-HIV pseudoviruses. Effects of the compounds on localization and activity of the viral ribonucleoprotein (RNP) were determined by immunofluorescence and an RNP minigenome assay, respectively. Results Among the alkaloids, lycorine ( AA1), hippeastrine ( AA2), hemanthamine ( AA3) and 11-hydroxy vittatine ( AA4) exhibited antiviral activities, with EC90 values of 0·52, 82·07, 4·15, and 13·45 μ m, respectively. These compounds did not affect the function of the outer membrane proteins or the viral entry process and viral RNP activity. As AA1 and AA3 exhibited stronger antiviral activities, they were further analyzed. Intracellular nucleoprotein (NP) localization showed that AA1 and AA3 inhibited the RNP complex in the nucleus at an early stage of a single-round and multi-round of replication. Conclusion Four Amaryllidaceae alkaloids were first determined that could exert anti-influenza activities after virus entry into cells. Furthermore, AA1 and AA3 could inhibit nuclear-to-cytoplasmic export of the RNP complex of virus replication. Thus, these compounds may be developed further as anti-influenza drug candidates. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Kelly et al. (2012) The significance of increased influenza notifications during spring and summer of 2010-11 in Australia. Influenza and Other Respiratory Viruses. DOI: 10.1111/irv.12057. Background & objective During the temperate out-of-season months in Australia in late 2010 and early 2011, an unprecedented high number of influenza notifications were recorded. We aimed to assess the significance of these notifications. Methods For Australia, we used laboratory-confirmed cases notified to the WHO FluNet surveillance tool; the percentage of these that were positive; notifications by state and influenza type and subtype; and surveillance data from Google FluTrends. For the state of Victoria, we used laboratory-confirmed notified cases and influenza-like illness (ILI) proportions. We compared virus characterisation using haemagglutination-inhibition assays and phylogenetic analysis of the haemagglutinin gene for seasonal and out-of-season notifications. Results The increase in notifications was most marked in tropical and subtropical Australia, but the number of out-of-season notifications in temperate Victoria was more than five times higher than the average of the previous three seasons. However, ILI proportions in spring-summer were not different to previous years. All out-of-season viruses tested were antigenically and genetically similar to those tested during either the 2010 or 2011 influenza seasons. An increase in the number of laboratories testing for influenza has led to an increase in the number of tests performed and cases notified. Conclusion An increase in influenza infections in spring-summer of 2010-11 in tropical and temperate Australia was not associated with any differences in virus characterisation compared with viruses that circulated in the preceding and following winters. This increase probably reflected a natural variation in out-of-season virus circulation, which was amplified by increased laboratory testing. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Li et al. (2012) Immunogenicity and safety of a 2009 pandemic influenza A (H1N1) monovalent vaccine in Chinese infants aged 6-35 months: a randomized, double-blind, controlled phase I clinical trial. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12028. Objectives The goal of this double-blind, randomized, controlled clinical trial was to assess the safety and immunogenicity of two different doses of a monovalent split-virion 2009 pandemic influenza A/H1N1 vaccine without adjuvant in Chinese infants aged 6-35 months. Design and setting Subjects were randomly assigned to receive either a 2009 pandemic (H1N1) vaccine containing 7.5 or 15 μg haemagglutinin (HA) or a seasonal influenza vaccine. 2 doses of the H1N1 vaccines or the seasonal influenza vaccine were given 21 days apart in younger infants aged 6-23 months or older infants aged 24-35 months. Sample Serum samples were collected immediately before the first injection and before and 21 days after the second injection. Main outcome measures Primary outcomes were haemagglutinin inhibition (HI) antibody responses 21 days following each vaccination. Safety was monitoring throughout the study. Results The first vaccination of 7.5 μg and 15 μg H1N1 vaccine induced seroprotective antibody titers (HI titers ≥ 1: 40) in 42.9-57.4% of younger infants and 49.1-61.0% older infants. Immune responses after completion of the two dose schedule were comparable in both age groups with seroprotective rates of 91-98% in each vaccine and age group and GMTs of 173-263. The H1N1 vaccine elicited similar rates of local and systemic adverse reactions as the seasonal influenza vaccine. Conclusions The 2009 pandemic influenza A /H1N1 vaccine were highly immunogenic in infants aged 6-35 months, and displayed a safety and reactogenicity profile similar to the seasonal influenza vaccine. Trial registration ClinicalTrial.gov identifier: NCT01047202 [ABSTRACT FROM AUTHOR]

Please cite this paper as: Khandaker et al. (2012) Comparing the use of, and considering the need for, lumbar puncture in children with influenza or other respiratory virus infections. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12039. Background The clinical presentation of influenza in infancy may be similar to serious bacterial infection and be investigated with invasive procedures like lumbar puncture (LP), despite very limited evidence that influenza occurs concomitantly with bacterial meningitis, perhaps because the diagnosis of influenza is very often not established when the decision to perform LP is being considered. Methods A retrospective medical record review was undertaken in all children presenting to the Children's Hospital at Westmead, Sydney, Australia, in one winter season with laboratory-confirmed influenza or other respiratory virus infections (ORVIs) but excluding respiratory syncytial virus, to compare the use of, and reflect on the need for, the performance of invasive diagnostic procedures, principally LP, but also blood culture, in influenza and non-influenza cases. We also determined the rate of concomitant bacterial meningitis or bacteraemia. Findings Of 294 children, 51% had laboratory-confirmed influenza and 49% had ORVIs such as parainfluenza viruses (34%) and adenoviruses (15%). Of those with influenza, 18% had a LP and 71% had a blood culture performed compared with 6·3% and 55·5% in the ORVI group (for both P < 0·01). In multivariate analysis, diagnosis of influenza was a strong independent predictor of both LP ( P = 0·02) and blood culture ( P = 0·05) being performed, and, in comparison with ORVIs, influenza cases were almost three times more likely to have a LP performed on presentation to hospital. One child with influenza (0·9%) had bacteraemia and none had meningitis. Interpretation Children with influenza were more likely to undergo LP on presentation to hospital compared with those presenting with ORVIs. If influenza is confirmed on admission by near-patient testing, clinicians may be reassured and less inclined to perform LP, although if meningitis is clinically suspected, the clinician should act accordingly. We found that the risk of bacterial meningitis and bacteraemia was very low in hospitalised children with influenza and ORVIs. A systematic review should be performed to investigate this across a large number of settings. [ABSTRACT FROM AUTHOR]

Healthcare workers ( HCWs) are at increased risk of exposure to respiratory pathogens and may transmit infection to vulnerable patients. This study summarises a recent systematic review, which aimed to assess evidence that influenza or pneumococcal vaccination of HCWs provides indirect protection for those patients most at risk of severe or complicated acute respiratory infection. A number of healthcare databases and sources of grey literature were searched using a predefined strategy, and citations screened for eligibility in accordance with specified inclusion criteria. Risk of bias was assessed using validated tools and results summarised qualitatively. Twenty papers were included in the final review, all of which considered influenza vaccination of HCW. As such, planned subanalysis of pneumococcal vaccination was discarded. The majority of primary research studies included (11/14) were conducted in long-term care facilities, but there was marked heterogeneity in terms of the population, intervention/exposure and outcomes considered. Consistency in the direction of effect was observed across several different outcome measures, suggesting that influenza vaccination of HCWs is likely to offer some protection. Further evidence is, however, required from acute care settings. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Kennedy et al. for the 2009 Pandemic H1N1 Influenza-Associated Lower Respiratory Tract Hemorrhage Working Group. (2012) Lower respiratory tract hemorrhage associated with 2009 pandemic influenza A (H1N1) virus infection. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12022. Background Influenza-associated lower respiratory tract hemorrhage (LRTH) has been reported in previous pandemics and is a rare complication of seasonal influenza virus infection. We describe patients with LRTH associated with 2009 pandemic influenza A (H1N1) (pH1N1) virus infection identified from April 2009 to April 2010 in the United States. Methods We ascertained patients with pH1N1-associated LRTH through state and local surveillance, the Emerging Infections Program, and CDCs Infectious Diseases Pathology Branch. All patients had influenza A, evidence of pneumonia, and evidence of LRTH. Results We identified 44 cases; the median number of days from illness onset to clinical signs of LRTH was one. Hemoptysis or respiratory tract bleeding was documented in 40% of pH1N1-associated LRTH cases, often present early during the course of illness. Twenty-one (48%) patients with LRTH had no other hemorrhagic diatheses. Seven (23%) patients with LRTH received antiviral treatment within two days of illness onset. Conclusions During influenza season, clinicians should consider influenza infection in the differential diagnosis for patients presenting with hemoptysis or other signs or symptoms of LRTH. While the impact of timing of antiviral therapy on this complication has not been studied, the rapid progression of LRTH may support use of early empiric therapy. Continued investigation is necessary to betterdefine the clinical spectrum of both seasonal influenza- and pH1N1-associated LRTH. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Schanzer et al. (2012) Statistical estimates of respiratory admissions attributable to seasonal and pandemic influenza for Canada. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12011. Background The number of admissions to hospital for which influenza is laboratory confirmed is considered to be a substantial underestimate of the true number of admissions due to an influenza infection. During the 2009 pandemic, testing for influenza in hospitalized patients was a priority, but the ascertainment rate remains uncertain. Methods The discharge abstracts of persons admitted with any respiratory condition were extracted from the Canadian Discharge Abstract Database, for April 2003-March 2010. Stratified, weekly admissions were modeled as a function of viral activity, seasonality, and trend using Poisson regression models. Results An estimated 1 out of every 6·4 admissions attributable to seasonal influenza (2003-April 2009) were coded to J10 (influenza virus identified). During the 2009 pandemic (May-March 2010), the influenza virus was identified in 1 of 1·6 admissions (95% CI, 1·5-1·7) attributed to the pandemic strain. Compared with previous H1N1 seasons (2007/08, 2008/09), the influenza-attributed hospitalization rate for persons <65 years was approximately six times higher during the 2009 H1N1 pandemic, whereas for persons 75 years or older, the pandemic rate was approximately fivefold lower. Conclusions Case ascertainment was much improved during the pandemic period, with under ascertainment of admissions due to H1N1/2009 limited primarily to patients with a diagnosis of pneumonia. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Azziz-Baumgartner et al. (2012) Incidence of influenza-associated mortality and hospitalizations in Argentina during 2002-2009. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12022. Background We estimated rates of influenza-associated deaths and hospitalizations in Argentina, a country that recommends annual influenza vaccination for persons at high risk of complications from influenza illness. Methods We identified hospitalized persons and deaths in persons diagnosed with pneumonia and influenza (P&I, ICD-10 codes J10-J18) and respiratory and circulatory illness (R&C, codes I00-I99 and J00-J99). We defined the influenza season as the months when the proportion of samples that tested positive for influenza exceeded the annual median. We used hospitalizations and deaths during the influenza off-season to estimate, using linear regression, the number of excess deaths that occurred during the influenza season. To explore whether excess mortality varied by sex and whether people were age <65 or ≥65 years, we used Poisson regression of the influenza-associated rates. Results During 2002-2009, 2411 P&I and 8527 R&C mean excess deaths occurred annually from May to October. If all of these excess deaths were associated with influenza, the influenza-associated mortality rate was 6/100 000 person-years (95% CI 4-8/100 000 person-years for P&I and 21/100 000 person-years (95% CI 12-31/100 000 person-years) for R&C. During 2005-2008, we identified an average of 7868 P&I excess hospitalizations and 22 994 R&C hospitalizations per year, resulting in an influenza-associated hospitalization rate of 2/10 000 person-years (95% CI 1-3/10 000 person-years) for P&I and 6/10 000 person-years (95% CI 3-8/10 000 person-years) for R&C. Conclusion Our findings suggest that annual rates of influenza-associated hospitalizations and death in Argentina were substantial and similar to neighboring Brazil. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Warren-Gash et al. (2012) Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12015. Hand hygiene may be associated with modest protection against some acute respiratory tract infections, but its specific role in influenza transmission in different settings is unclear. We aimed to review evidence that improving hand hygiene reduces primary and secondary transmission of (i) influenza and (ii) acute respiratory tract infections in community settings. We searched Medline, Embase, Global Health and Cochrane databases up to 13 February 2012 for reports in any language of original research investigating the effect of hand hygiene on influenza or acute respiratory tract infection where aetiology was unspecified in community settings including institutions such as schools, and domestic residences. Data were presented and quality rated across outcomes according to the Grading of Recommendations Assessment, Development and Evaluation system. Sixteen articles met inclusion criteria. There was moderate to low-quality evidence of a reduction in both influenza and respiratory tract infection with hand hygiene interventions in schools, greatest in a lower-middle-income setting. There was high-quality evidence of a small reduction in respiratory infection in childcare settings. There was high-quality evidence for a large reduction in respiratory infection with a hand hygiene intervention in squatter settlements in a low-income setting. There was moderate- to high-quality evidence of no effect on secondary transmission of influenza in households that had already experienced an index case. While hand hygiene interventions have potential to reduce transmission of influenza and acute respiratory tract infections, their effectiveness varies depending on setting, context and compliance. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Adhin et al. (2012) Trends of Influenza infection in Suriname. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12037. The trends of influenza infection in Suriname were assessed from February 2010 through February 2011. Testing of 393 patients with symptoms of acute respiratory infection (ARI) revealed 15·3% Influenza B and 18·6% could be identified as influenza A positive, consisting of 56% influenza A(H1N1)pdm09 and 44% seasonal A(H3N2). Influenza infection occurred throughout the year, and all three influenza types affected young children as the primary population. The annual incidence of A(H1N1)pdm09 was 6·88 per 100 000 inhabitants [CI] 4·87-9·45. The spread of influenza could neither be linked to tourist flow from the Netherlands nor to contact rates related to school schedules. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Charland et al.(2012) Relationship between community prevalence of obesity and associated behavioral factors and community rates of influenza-related hospitalizations in the United States. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12019. Background Findings from studies examining the association between obesity and acute respiratory infection are inconsistent. Few studies have assessed the relationship between obesity-related behavioral factors, such as diet and exercise, and risk of acute respiratory infection. Objective To determine whether community prevalence of obesity, low fruit/vegetable consumption, and physical inactivity are associated with influenza-related hospitalization rates. Methods Using data from 274 US counties, from 2002 to 2008, we regressed county influenza-related hospitalization rates on county prevalence of obesity (BMI ≥ 30), low fruit/vegetable consumption (<5 servings/day), and physical inactivity (<30 minutes/month recreational exercise), while adjusting for community-level confounders such as insurance coverage and the number of primary care physicians per 100 000 population. Results A 5% increase in obesity prevalence was associated with a 12% increase in influenza-related hospitalization rates [adjusted rate ratio (ARR) 1·12, 95% confidence interval (CI) 1·07, 1·17]. Similarly, a 5% increase in the prevalence of low fruit/vegetable consumption and physical inactivity was associated with an increase of 12% (ARR 1·12, 95% CI 1·08, 1·17) and 11% (ARR 1·11, 95% CI 1·07, 1·16), respectively. When all three variables were included in the same model, a 5% increase in prevalence of obesity, low fruit/vegetable consumption, and physical inactivity was associated with 6%, 8%, and 7% increases in influenza-related hospitalization rates, respectively. Conclusions Communities with a greater prevalence of obesity were more likely to have high influenza-related hospitalization rates. Similarly, less physically active populations, with lower fruit/vegetable consumption, tended to have higher influenza-related hospitalization rates, even after accounting for obesity. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Kelly et al. Moderate influenza vaccine effectiveness with variable effectiveness by match between circulating and vaccine strains in Australian adults aged 20-64 years, 2007-2011. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12018. Background Influenza vaccines are licensed annually based on immunogenicity studies. We used five sequential years of data to estimate influenza vaccine effectiveness (VE), the critical outcome in the field. Methods Between 2007 and 2011, we performed annual prospective test-negative design case-control studies among adults aged 20-64 years recruited from sentinel general practices in the Australian state of Victoria. We used PCR-confirmed influenza as the endpoint to estimate influenza VE for all years. We compared annual VE estimates with the match between circulating and vaccine strains, determined by haemagglutination inhibition assays. Results The adjusted VE estimate for all years (excluding 2009) was 62% (95% CI 43, 75). By type and subtype, the point estimates of VE by year ranged between 31% for seasonal influenza A(H1N1) and 88% for influenza A(H1N1)pdm09. In 2007, when circulating strains were assessed as incompletely matched, the point estimate of the adjusted VE against all influenza was 58%. The point estimate was 59% in 2011 when all strains were assessed as well matched. Conclusion Trivalent inactivated vaccines provided moderate protection against laboratory-confirmed influenza in adults of working age, although VE estimates were sensitive to the model used. VE estimates correlated poorly with circulating strain match, as assessed by haemagglutination inhibition assays, suggesting a need for VE studies that incorporate antigenic characterization data. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Cuevas et al. (2013) Spread of different rhinovirus B genotypes in hospitalized children in Spain. Influenza and Other Respiratory Viruses 7(5), 623-628. Human Rhinovirus (HRV) classification is an evolving process. New genotypes have been described within HRV-A and HRV-C species, but only one has been accepted related to HRV-B. From 2003 to 2010, a total of 3987 nasopharyngeal aspirate samples were taken from pediatric patients admitted to the Severo Ochoa Hospital in Madrid (Spain). After viral analysis, 949 (23·8%) tested positive to HRV. A random selection of 397 (42%) positive samples showed that 39 (9·8%) were HRV-B. The sequencing of partial VP4/VP2 coding region revealed the spread of 13 of 25 defined HRV-B serotypes and three putative new genotypes. Such results remark the high diversity of HRV-B. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Fitter et al. (2012) Pandemic H1N1 influenza surveillance in Haiti, July-December 2009. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12060. From June 2009 through December 2009, Haiti conducted sentinel surveillance for influenza. 499 samples were collected and tested using real-time RT-PCR. 197 (39.5%) were positive for influenza, including 95 (48%) pandemic (H1N1) 2009, 57 (29%) seasonal influenza A and 45 (23%) influenza B. The median age of pandemic (H1N1) 2009 cases was 21.7; two-thirds of pandemic (H1N1) 2009 cases were in patients aged 6 years - 35 years. Pandemic activity peaked in September and co-circulated with other influenza subtypes. The age distribution and seasonality of pandemic (H1N1) 2009 in Haiti were similar to other countries in the Caribbean region. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Fox et al. (2012) Adjuvanted pandemic influenza vaccine: variation of emulsion components affects stability, antigen structure, and vaccine efficacy. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12031. Abstract Background Adjuvant formulations are critical components of modern vaccines based on recombinant proteins, which are often poorly immunogenic without additional immune stimulants. Oil-in-water emulsions comprise an advanced class of vaccine adjuvants that are components of approved seasonal and pandemic influenza vaccines. However, few reports have been published that systematically evaluate the in vitro stability and in vivo adjuvant effects of different emulsion components. Objectives To evaluate distinct classes of surfactants, oils, and excipients, for their effects on emulsion particle size stability, antigen structural interactions, and in vivo activity when formulated with a recombinant H5N1 antigen. Methods Emulsions were manufactured by high pressure homogenization and characterized alone or in the presence of vaccine antigen by dynamic light scattering, zeta potential, viscosity, pH, hemolytic activity, electron microscopy, fluorescence spectroscopy, and SDS-PAGE. In vivo vaccine activity in the murine model was characterized by measuring antibody titers, antibody-secreting plasma cells, hemagglutination inhibition titers, and cytokine production. Results We demonstrate that surfactant class and presence of additional excipients are not critical for biological activity, whereas oil structure is crucial. Moreover, we report that simplified two-component emulsions appear more stable by particle size than more complex formulations.Finally, differences in antigen structural interactions with the various emulsions do not appear to correlate with in vivo activity. Conclusions Oil-in-water emulsions can significantly enhance antibody and cellular immune responses to a pandemic influenza antigen. The dramatic differences in adjuvant activity between squalene-based emulsion and medium chain triglyceride-based emulsion are due principally to the biological activity of the oil composition rather than physical interactions of the antigen with the emulsion. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Sarah C. Gilbert. (2012) Advances in the development of universal influenza vaccines. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12013. Despite the widespread availability and use of influenza vaccines, influenza still poses a considerable threat to public health. Vaccines against seasonal influenza do not offer protection against pandemic viruses, and vaccine efficacy against seasonal viruses is reduced in seasons when the vaccine composition is not a good match for the predominant circulating viruses. Vaccine efficacy is also reduced in older adults, who are one of the main target groups for vaccination. The continual threat of pandemic influenza, with the known potential for rapid spread around the world and high mortality rates, has prompted researchers to develop a number of novel approaches to providing immunity to this virus, focusing on target antigens which are highly conserved between different influenza A virus subtypes. Several of these have now been taken into clinical development, and this review discusses the progress that has been made, as well as considering the requirements for licensing these new vaccines and how they might be used in the future. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Quintana et al. (2012) Influence of renal replacement therapy on immune response after one and two doses of the A(H1N1) pdm09 vaccine. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12024. Background Patients with end-stage renal disease have a reduced response to vaccination because of the general suppression of the immune system associated with uraemia. Objectives We evaluated the immune response and differential factors in the immunogenecity to an adjuvanted A(H1N1) pdm09 vaccine (Pandemrix®) in four populations of renal patients after one and two doses of vaccine. Patients Methods 151 patients were included in this study: 58 chronic haemodialysis patients, 52 renal allograft recipients, 14 peritoneal dialysis patients and 27 patients with advanced chronic kidney disease in preparation for kidney replacement therapy. Influenza-specific antibody levels were measured by monitoring A(H1N1) pdm09 titres using a haemagglutination inhibition assay. Results The seroconversion rate at 42 days after two vaccine doses was 80% in the haemodialysis group, 64·9% in the renal allograft recipients group, 100% in the advanced chronic kidney disease group and 71·4% in the peritoneal dialysis group ( P = 0·041). Conclusions Immune response to two doses of the influenza A H1N1 vaccine is dissimilar in the four renal conditions, confirming that seroprotection in pre-dialysis, haemodialysis and peritoneal dialysis is similar to that in the general population vaccinated with one dose. In contrast, renal transplant recipients with good allograft function showed inadequate protection and triple immunosuppressive therapy including calcineurin inhibitors, mycophenolate and steroids negatively influenced seroconversion after vaccination in renal recipients. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Dapat et al. (2012) Delayed emergence of oseltamivir-resistant seasonal influenza A (H1N1) and pandemic influenza A(H1N1)pdm09 viruses in Myanmar. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12030. The prevalence and timing of emergence of oseltamivir-resistant seasonal and pandemic influenza A (H1N1) viruses in Myanmar in 2008 and 2009 are described in this report. In 2008, the oseltamivir-resistant seasonal H1N1 virus was detected at a lower rate (6%) and emerged at least 2 months later when compared with neighboring countries. Similarly, the prevalence of pandemic H1N1 virus was low (3%) and the timing of emergence was late (August 2009) in Myanmar. Interestingly, we detected three isolates that were resistant to both amantadine and oseltamivir. Limited movement of people into the country is attributed to the delayed emergence of drug-resistant seasonal and pandemic A(H1N1) viruses. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Larcombe et al. (2012) Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12012. Background Exposure to diesel exhaust particles (DEP) is thought to exacerbate many pre-existing respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease, however, there is a paucity of data on whether DEP exacerbates illness due to respiratory viral infection. Objectives To assess the physiological consequences of an acute DEP exposure during the peak of influenza-induced illness. Methods We exposed adult female BALB/c mice to 100 μg DEP (or control) 3·75 days after infection with 104·5 plaque forming units of influenza A/Mem71 (or control). Six hours, 24 hours and 7 days after DEP exposure we measured thoracic gas volume and lung function at functional residual capacity. Bronchoalveolar lavage fluid was taken for analyses of cellular inflammation and cytokines, and whole lungs were taken for measurement of viral titre. Results Influenza infection resulted in significantly increased inflammation, cytokine influx and impairment to lung function. DEP exposure alone resulted in less inflammation and cytokine influx, and no impairment to lung function. Mice infected with influenza and exposed to DEP had higher viral titres and neutrophilia compared with infected mice, yet they did not have more impaired lung mechanics than mice infected with influenza alone. Conclusions A single dose of DEP is not sufficient to physiologically exacerbate pre-existing respiratory disease caused by influenza infection in mice. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Ducatez et al. (2012) Long-term vaccine-induced heterologous protection against H5N1 influenza viruses in the ferret model. Influenza and Other Respiratory Viruses 7(4), 506-512. Background Highly pathogenic H5N1 influenza viruses reemerged in humans in 2003 and have caused fatal human infections in Asia and Africa as well as ongoing outbreaks in poultry. These viruses have evolved substantially and are now so antigenically varied that a single vaccine antigen may not protect against all circulating strains. Nevertheless, studies have shown that substantial cross-reactivity can be achieved with H5N1 vaccines. These studies have not, however, addressed the issue of duration of such cross-reactive protection. Objectives To directly address this using the ferret model, we used two recommended World Health Organization H5N1 vaccine seed strains - A/Vietnam/1203/04 (clade 1) and A/duck/Hunan/795/02 (clade 2.1) - seven single, double, or triple mutant viruses based on A/Vietnam/1203/04, and the ancestral viruses A and D, selected from sequences at nodes of the hemagglutinin and neuraminidase gene phylogenies to represent antigenically diverse progeny H5N1 subclades as vaccine antigens. Results All inactivated whole-virus vaccines provided full protection against morbidity and mortality in ferrets challenged with the highly pathogenic H5N1 strain A/Vietnam/1203/04 5 months and 1 year after immunization. Conclusion If an H5N1 pandemic was to arise, and with the hypothesis that one can extrapolate the results from three doses of a whole-virion vaccine in ferrets to the available split vaccines for use in humans, the population could be efficiently immunized with currently available H5N1 vaccines, while the homologous vaccine is under production. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Bali NK et al. (2012) Knowledge, attitude, and practices about the seasonal influenza vaccination among healthcare workers in Srinagar, India. Influenza and Other Respiratory Viruses 7(4), 540-545. Background Healthcare workers (HCWs) universally have a poor uptake of influenza vaccination. However, no data are available from India. Objective To explore knowledge, attitudes, and practices associated with influenza vaccination in HCWs in a temperate climate area in northern India. Patients and Methods A self-administered questionnaire was offered to all HCWs in three major hospitals of Srinagar and information sought on motivations, perceptions, preferences and practices regarding influenza vaccination. Results Of the 1750 questionnaires received, 1421 (81%) were returned. Only 62 (4·4%) HCWs had ever received influenza vaccination even as 1348 (95%) believed that influenza poses adverse potential consequences for themselves or their contacts; 1144 (81%) were aware of a vaccine against influenza and 830 (58%) of its local availability. Reasons cited by 1359 participants for not being vaccinated included ignorance about vaccine availability (435; 32%), skepticism about efficacy (248; 18%), busy schedule (166; 12%), fear of side effects (70; 4%), and a perception of not being-at-risk (82; 6%). Sixty-one percent (865) believed that vaccine programs are motivated by profit. Eighty-eight percent opined for mandatory vaccination for HCWs caring for the high-risk patients, as a part of 'employee health program'. Most of the participants intended to get vaccinated in the current year even as 684 (48%) held that vaccines could cause unknown illness and 444 (31%) believed their adverse effects to be underreported. Conclusion Influenza vaccination coverage among HCWs is dismally low in Srinagar; poor knowledge of vaccine availability and misperceptions about vaccine effectiveness, fear of adverse effects and obliviousness to being-at-risk being important barriers. Multifaceted, adaptable measures need to be invoked urgently to increase the coverage. [ABSTRACT FROM AUTHOR]